Related papers: A straightforward meta-analysis approach for oncol…
In response to the U.S.\ Food and Drug Administration's (FDA) Project Optimus, a paradigm shift is underway in the design of early-phase oncology trials. To accelerate drug development, seamless Phase I/II designs have gained increasing…
Identifying subgroups, which respond differently to a treatment, both in terms of efficacy and safety, is an important part of drug development. A well-known challenge in exploratory subgroup analyses is the small sample size in the…
We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a…
In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study…
The tolerancing step has a great importance in the design process. It characterises the relationship between the different sectors of the product life cycle: Design, Manufacturing and Control. We can distinguish several methods to assist…
We propose a rule-based statistical design for combination dose-finding trials with two agents. The Ci3+3 design is an extension of the i3+3 design with simple decision rules comparing the observed toxicity rates and equivalence intervals…
Personalized cancer treatments based on the molecular profile of a patient's tumor are an emerging and exciting class of treatments in oncology. As genomic tumor profiling is becoming more common, targeted treatments to specific molecular…
Traditional phase I dose finding cancer clinical trial designs aim to determine the maximum tolerated dose (MTD) of the investigational cytotoxic agent based on a single toxicity outcome, assuming a monotone dose-response relationship.…
A hierarchical logistic regression Bayesian model is proposed and implemented in R to model the probability of patient improvement corresponding to any given dosage of a certain drug. RStan is used to obtain samples from the posterior…
Drug discovery is a multi-stage process that comprises two costly major steps: pre-clinical research and clinical trials. Among its stages, lead optimization easily consumes more than half of the pre-clinical budget. We propose a combined…
Statistical methodology for the design and analysis of clinical Phase II dose response studies, with related software implementation, are well developed for the case of a normally distributed, homoscedastic response considered for a single…
Meta-analysis is commonly used to combine results from multiple clinical trials, but traditional meta-analysis methods do not refer explicitly to a population of individuals to whom the results apply and it is not clear how to use their…
We examine nonparametric dose-finding designs that use toxicity estimates based on all available data at each dose allocation decision. We prove that one such design family, called here "interval design", converges almost surely to the…
Two useful strategies to speed up drug development are to increase the patient accrual rate and use novel adaptive designs. Unfortunately, these two strategies often conflict when the evaluation of the outcome cannot keep pace with the…
Incorporating preclinical animal data, which can be regarded as a special kind of historical data, into phase I clinical trials can improve decision making when very little about human toxicity is known. In this paper, we develop a robust…
In preclinical investigations, e.g. in in vitro, in vivo and in silico studies, the pharmacokinetic, pharmacodynamic and toxicological characteristics of a drug are evaluated before advancing to first-in-man trial. Usually, each study is…
Drug-drug interactions (DDIs) are a leading cause of preventable adverse events, often complicating treatment and increasing healthcare costs. At the same time, knowing which drugs do not interact is equally important, as such knowledge…
In the era of targeted therapy, there has been increasing concern about the development of oncology drugs based on the "more is better" paradigm, developed decades ago for chemotherapy. Recently, the US Food and Drug Administration (FDA)…
In oncology, phase II or multiple expansion cohort trials are crucial for clinical development plans. This is because they aid in identifying potent agents with sufficient activity to continue development and confirm the proof of concept.…
Meta-analysis employs statistical techniques to synthesize the results of individual studies, providing an estimate of the overall effect size for a specific outcome of interest. The direction and magnitude of this estimate, along with its…